Systems and methods for analyzing substances using a mass spectrometer

ABSTRACT

Systems and methods for analyzing compounds in a sample. In one embodiment, the present technology is directed towards a method of analyzing a sample, comprising: emitting ions from the sample; selectively filtering the emitted ions for at least one designated trigger ion; fragmenting the designated trigger ions; scanning for a designated trigger ion fragment; and upon detecting the designated trigger ion fragment, scanning for at least one confirmatory ion fragment.

CROSS-REFERENCE TO RELATED APPLICATION

The present application is a divisional of U.S. patent application Ser.No. 12/402/954, filed Mar. 12, 2009, and claims priority from U.S.provisional patent application No. 61/038,068, filed Mar. 20, 2008, bothof which are incorporated herein by reference in their entireties.

BACKGROUND OF THE INVENTION

1. Field

The present application relates generally to the field of massspectrometry.

2. Background

The analysis of a substance to determine its composition may benecessary for many applications, including toxicology, forensics andenvironmental testing, as well as food and drug research. Often, samplesto be analyzed are analyzed for the presence of numerous differentanalytes of interest. Such samples may, for example, be in the form ofbodily fluids taken from test subjects, which fluids often include bothdrug metabolites of interest, as well as irrelevant endogenous ions fromthe test subject. Correctly determining the presence or absence of alarge number of analytes of interest from complex substances can bedifficult and time-consuming.

Mass spectrometers are often used for producing a mass spectrum of asample to find its composition. This is normally achieved by ionizingthe sample and separating ions of differing masses and recording theirrelative abundance by measuring intensities of ion flux. For example,with time-of-flight mass spectrometers, ions are pulsed to travel apredetermined flight path. The ions are then subsequently recorded by adetector. The amount of time that the ions take to reach the detector,the “time-of-flight”, may be used to calculate the ion's mass to chargeratio, m/z.

Additional information (in addition to an ion's precursor mass) can thenbe obtained by fragmenting the ion via CID (collision induceddissociation) in a collision cell (or other mean) to generate an MSMSspectrum. In most instruments with MSMS capabilities, the process ofgenerating a mass spectrum, selecting a precursor ion and generating anMSMS (mass spectrum/mass spectrum) spectrum can be performed in anautomated mode. This mode of acquisition is frequently referred to asInformation Dependant Acquisition (IDA) or Data Dependant Experiment(DDE).

Chromatographic equipment such as a liquid chromatograph may be used toelute or release ions from a sample into the mass spectrometer over aperiod of time. Multiple reaction monitoring (MRM) or otherdistributed-analysis and recursive techniques may be used to analyze theions received by the mass spectrometer.

Previous MRM techniques involve repeated cycles of scans by the massspectrometer for predetermined analytes of interest. A “duty cycle”would involve a list of analytes to be “cycled through” and scanned forby the mass spectrometer. During MRM analysis, the mass spectrometerwould divide its scans equally amongst the analytes of interest in theduty cycle. As a result, such duty cycles have a practical upper limitin the number of analytes which may be scanned for. Once the number ofanalytes grows too large (for example, some mass spectrometers requireduty cycles to have no more than 50 analytes of interest in order tomaintain acceptable data quality), the amount of scan time available foreach analyte of interest is insufficient to provide accurate data.

The applicants have accordingly recognized a need for systems andmethods for analyzing and identifying ions from samples.

SUMMARY OF THE INVENTION

In one aspect, the present technology is directed towards a system foranalyzing analytes in a sample. The system comprises an ion source foremitting ions from the sample; a mass spectrometer adapted to receivethe ions from the ion source; a controller operatively coupled to themass spectrometer and configured to control the first mass filter tofilter for a designated ion of interest and to control the second massfilter to filter for a designated ion fragment of interest; and atrigger data set having at least one trigger entry. It should beunderstood that “ion fragment(s)” as used herein, are themselves ionsand could alternately be referred to as “fragment ion(s)”.

The mass spectrometer includes: a first mass filter to filter ionsreceived from the ion source, an ion fragmenter configured to fragmentions received from the first mass filter, a second mass filterconfigured to filter ion fragments received from the ion fragmenter, andat least one detector configured to detect ion fragments received fromthe second mass filter. As well, each trigger entry includes: adesignated trigger ion, a designated trigger ion fragment, a triggertime window, and a confirmatory data set. In turn, each confirmatorydata set has at least one confirmatory entry, and each confirmatoryentry includes: a designated confirmatory ion, and a designatedconfirmatory ion fragment. The controller is responsive to the triggerdata set, and during the trigger time window for each trigger entry thecontroller is configured to control the first mass filter to filter forthe corresponding designated trigger ion and to control the second massfilter to filter for the corresponding designated trigger ion fragment.Additionally, upon detection of the designated trigger ion fragment bythe detector, the controller is configured to control the first massfilter to filter for the designated confirmatory ion and to control thesecond mass filter to filter for the designated confirmatory ionfragment.

The system may also include data storage operatively coupled to thecontroller, wherein the data storage is configured to store datacorresponding to the ion fragments detected by the detector. As well,the trigger data set may comprises a plurality of trigger entries.Additionally, at least one confirmatory data set may comprise aplurality of confirmatory entries. Furthermore, the ion source maycomprise a liquid chromatograph.

In another aspect, the technology is directed towards a system foranalyzing ions emitted from an ion source. The system comprises: a firstmass filter adapted to receive and to filter ions from the ion source,an ion fragmenter configured to fragment ions received from the firstmass filter, a second mass filter configured to filter ion fragmentsreceived from the ion fragmenter, and a detector configured to detection fragments received from the second mass filter. The system alsoincludes: a controller operatively coupled to the first and second massfilters, to the fragmenter and to the detector, wherein the controlleris configured to control the first mass filter to filter for adesignated ion of interest and to control the second mass filter tofilter for a designated ion fragment of interest; a trigger data sethaving at least one trigger entry; and a confirmatory data set for eachtrigger entry. Each trigger entry includes: a designated trigger ion, adesignated trigger ion fragment, and a trigger time window. Eachconfirmatory data set has at least one confirmatory entry, and eachconfirmatory entry includes: a designated confirmatory ion, and adesignated confirmatory ion fragment.

The controller is responsive to the trigger data set and to theconfirmatory data set, and during the trigger time window for eachtrigger entry the controller is configured to control the first massfilter to filter for the corresponding designated trigger ion and tocontrol the second mass filter to filter for the correspondingdesignated trigger ion fragment. Upon detection of the designatedtrigger ion fragment by the detector, the controller is configured tocontrol the first mass filter to filter for the designated confirmatoryion and to control the second mass filter to filter for the designatedconfirmatory ion fragment.

The system may also comprise data storage operatively coupled to thecontroller, wherein the data storage is configured to store datacorresponding to the ion fragments detected by the detector. As well,the trigger data set may comprise a plurality of trigger entries.Furthermore, in some instances at least one confirmatory data setcomprises a plurality of confirmatory entries.

In yet a further aspect, the present technology is directed towards amethod of analyzing a sample, comprising: emitting ions from the sample;selectively filtering the emitted ions for at least one designatedtrigger ion; fragmenting the designated trigger ions; scanning for adesignated trigger ion fragment; and upon detecting the designatedtrigger ion fragment, scanning for at least one confirmatory ionfragment.

The method may also include performing the filtering, fragmenting,scanning, and detecting and scanning during a trigger time windowcorresponding to the designated trigger ion. The trigger time window maybe selected to correspond to a time period when the trigger ion isexpected to be emitted from the sample.

The filtering, fragmenting, scanning, and detecting and scanning may beperformed for a plurality of designated trigger ions during a pluralityof trigger time windows, each trigger time window corresponding to adesignated trigger ion. Each trigger time window may be selected tocorrespond to a time period when the corresponding trigger ion isexpected to be emitted from the sample. In some instances, the scanningmay be performed substantially simultaneously for at least two differentdesignated trigger ion fragments.

The method may further comprise generating a report containing datacorresponding to the detected designated trigger ion fragments andconfirmatory ion fragments.

In some instances, the method may involve using liquid chromatographyfor emitting ions.

In another aspect, the invention may be directed to computer readablemedia configured to cause a mass spectrometer having a computercontroller to perform the method.

BRIEF DESCRIPTION OF THE DRAWINGS

The present invention will now be described, by way of example only,with reference to the following drawings, in which like referencenumerals refer to like parts and in which:

FIG. 1 is a schematic diagram of a mass spectrometer made in accordancewith the present disclosure;

FIG. 2 is a is a representative example of a trigger data set as may bestored in the data storage of the mass spectrometer of FIG. 1;

FIG. 3A is a representative example of a first confirmatory data set asmay be stored in the data storage of the mass spectrometer of FIG. 1;

FIG. 3B is a representative example of a second confirmatory data set asmay be stored in the data storage of the mass spectrometer of FIG. 1;

FIG. 4A is a representative example of a duty cycle listing as may bestored in the data storage of the mass spectrometer of FIG. 1 at a firsttime during an analysis, in this example at or near the beginning of theanalysis period;

FIG. 4B is a representative example of a duty cycle listing as may bestored in the data storage of the mass spectrometer of FIG. 1 at asecond time during an analysis, after the duty cycles listing of FIG. 4Ahas been updated; and

FIG. 5 is a flow diagram illustrating the steps of a method of analyzinga compound in accordance with the present disclosure.

DESCRIPTION OF VARIOUS EMBODIMENTS

Referring to FIG. 1, illustrated therein is an analysis system referredto generally as 10, made in accordance with the present disclosure. Thesystem 10 is preferably configured to be capable of performinginformation dependent acquisition (IDA) in accordance with the presentdisclosure, as will be understood.

The analysis system 10 includes a mass spectrometer 11 (which may be anMS/MS system such as a quadrupole hybrid linear ion trap such as the4000QTRAP LC/MS/MS System sold by Applied Biosystems/MDS SCIEX). Thespectrometer 11 comprises a suitably programmed controller or centralprocessing unit (CPU) 12 having a programmed MRM trigger engine 14stored in RAM or other suitable computer-readable media which mayinclude a clock module 18. An input/output (I/O) device 16 (typicallyincluding an input component 16.sup.A such as a keyboard or controlbuttons, and an output component such as a display 16.sup.B) is alsooperatively coupled to the CPU 12. Data storage 17 is also preferablyprovided.

The system 10 also includes an ion source 20, configured to emit ions,generated from the sample 21 to be analyzed. The ion source 20 may be acontinuous ion source, for example, such as an electron impact, chemicalionization, or field ionization ion source (which may be used inconjunction with a gas chromatography source), or an electrospray oratmospheric pressure chemical ionization ion source (which may be usedin conjunction with a liquid chromatography source), or a desorptionelectrospray ionization (DESI), or a laser desorption ionization source,as will be understood. A laser desorption ionization source, such as amatrix assisted laser desorption ionization (MALDI) can typicallygenerate a series of pulses in which a pulsed beam of ions is emitted.

The ion source 20 can also be provided with an ion transmission ionguide, such as a multipole ion guide, ring guide, or an ion mass filter,such as a quadrupole mass filter, or an ion trapping device, asgenerally known in the art (not shown). For brevity, the term ion source20 has been used to describe the components which generate ions from thesample 21, and emit analyte ions of interest for detection. Other typesof ion sources 20 may also be used, such as a system having a tandemmass filter and ion trap. Preferred ion sources are those which emit theions from the sample 21 over a range of times, to enable recursive massanalysis by the mass spectrometer 11 using MRM or other suitabletechniques.

As will be understood, liquid chromatography may be used to separateions dissolved in solvent from other substances in the sample 21, andrelease or emit such ions for MS analysis. As a result of the differenttimings for the chemical interactions that take place during the LCphase, the reaction products (which include the ions or analytes ofinterest) are released over time. The release times for specificanalytes can be estimated, based on the expected chemical interactions.

As noted above, the spectrometer 11 may comprise a triple quadrupolemass spectrometer, having triple rod sets Q1, Q2 and Q3. The rod sets Q1and Q3 may be controlled by the processor 12 (via the trigger engine 14)to select or filter for ions having a particular m/z. In contrast, theQ2 rod set is provided with a chamber and configured to operate as acollision cell or fragmenter for fragmenting the ions received from Q1.The resulting ion fragments may be passed through to, and selectivelyfiltered by, rod set Q3, before being detected or recorded by thedetector 22.

Optics 24 or other focusing elements, such as an electrostatic lens canalso be disposed in the path of the emitted ions, typically between theQ3 rod set and the detector 22, for focusing the ions onto the detector22.

Referring now to FIG. 2, illustrated therein is a representative exampleof a trigger data set 200 as may be stored in the data storage 17. Thetrigger data set 200 includes at least one trigger entry 202, and eachtrigger entry 202 includes: at least one m/z value, each such m/z valuecorresponding to a designated trigger ion 204, at least one m/z value,each such m/z value corresponding to a designated trigger ion fragment206, timing data corresponding to a trigger time window 208, and linkingdata such as a unique identifier data 210 providing a link to aconfirmatory data set 300. As will be understood, each confirmatory dataset 300 need not be uniquely linked to only one designated trigger ion204/fragment 206 couplet. In some instances, such as in the case ofbackground noise or other interference, it may be desirable to have morethan one trigger ion 204/fragment 206 couplet detected before thecorresponding confirmatory data set 300 is filtered for, as will beunderstood.

As will also be understood, the trigger time window 208 corresponds to apredetermined period of time when the corresponding designated triggerion 204 is expected to be emitted by the ion source 20 from the sample21. It should also be understood that the trigger time or scanningwindow data 208 is not a requirement, as for certain simplifiedapplications, the “windows” may be treated as running for the entireanalysis period.

Illustrated in FIG. 3A is a representative example of a confirmatorydata set 300 as may be stored in the data storage 17. Each confirmatorydata set 300 has at least one confirmatory entry 302, and eachconfirmatory entry 302 includes: at least one m/z value, each such m/zvalue corresponding to a designated confirmatory ion 304, and at leastone m/z value, each such m/z value corresponding to a designatedconfirmatory ion fragment 306. Each confirmatory entry 302 may alsoinclude timing data corresponding to a confirmatory time window 308. Theexample confirmatory timing window data 308 corresponds to a duration ofscanning time (e.g. 5 seconds). As will be understood in the context ofthe discussion below, in some instances, while the commencement time ofan elution period may be uncertain, the duration of an elution periodcan often be estimated or known with greater accuracy. As a result, oncethe rising edge of an LC peak corresponding to the analyte of interesthas been detected in accordance with the method discussed below, thesystem 10 may scan for the confirmatory ion(s) 304 for the duration ofthe expected elution period.

Each confirmatory data entry 302 also includes a unique confirmatoryidentifier 310, corresponding to a confirmatory data identifier 210 inthe trigger data 200.

In alternate embodiments (not shown), the confirmatory time window data308 might match the corresponding trigger time window 208 periods. Insuch instances the confirmatory time window data 308 need not be storedin the confirmatory data set 300, and the corresponding trigger timewindow 208 data may be used by the CPU 12 as required.

Illustrated in FIG. 3B, is a representative example of an alternateconfirmatory data set 300B as may be stored in the data storage 17. Thealternate confirmatory data set 300B generally corresponds to theconfirmatory data set 300 and has at least one confirmatory entry 302,with each confirmatory entry 302 including: at least one m/z value, eachsuch m/z value corresponding to a designated confirmatory ion 304, andat least one m/z value, each such m/z value corresponding to adesignated confirmatory ion fragment 306. Each confirmatory entry 302also includes timing data corresponding to a confirmatory time windowdelay 308B.

As will be understood, for certain analysis applications, such asproteomics, in which qualification data is desired (i.e. a determinationas to the presence of a particular analyte of interest), it may beadvantageous to conduct a single scan (or limited number of scans) toconfirm the presence of the confirmatory ions 304 and confirmatory ionfragments 306. For example, while a trigger ion 204 will likely bedetected at the rising edge of the LC peak corresponding to the analyteof interest, the scanning for the corresponding confirmatory ion(s) 304and fragment(s) 306 may be delayed by the confirmatory time window delay308B to correspond to the expected LC peak apex, as will be understood.

Turning now to FIG. 4A, illustrated therein is a representative exampleof a duty cycle listing 400 as may be stored in the data storage 17 at afirst time during an analysis, in this example, at or near the beginningof the analysis period. Each duty cycle entry 402 in the duty cyclelisting 400 includes m/z data corresponding to a designated precursorion 404, an m/z value corresponding to a designated ion fragment 406,together with a corresponding scanning window timeframe 408. Illustratedin FIG. 4B is a representative example of the duty cycle listing 400′ asmay be stored in the data storage 17 at a second time during ananalysis, for example at about 8 seconds after the commencement of theanalysis period.

As will be understood, in operation, the CPU 12/MRM trigger engine 14 isresponsive to the trigger data set 200 and to the confirmatory data set300. As will be discussed in greater detail below, the trigger engine 14is configured to manage the duty cycle list 400 during MRM analysis,such that during the analysis period, designated precursor ion 404 andion fragment 406 couplets 402 are added to and removed from the dutycycle list 400 over time, based on the trigger 200 and confirmatory 300data sets, as well as the data received from the detector 22. In turn,the trigger engine 14 utilizes the ion/fragment couplets 404,406 in theduty cycle listing 400 to regulate the operation of the mass analyzersQ1 and Q3, to filter for the corresponding precursor ions 404 andconfirmatory ion fragments 406.

FIG. 5 sets out the steps of the method, referred to generally as 500,carried out by the spectrometer system 10 during an analysis period.Typically, before the analysis period is commenced, the analytes ofinterest are determined (for which the sample is being analyzed)(Block502). As noted above, for each analyte of interest, one or more coupletseach comprising a designated precursor ion 204 and correspondingdesignated ion fragment 206 may be stored in a trigger entry 202 in thetrigger data set 200. The corresponding trigger time window 208, is alsodetermined and stored (Block 504).

The confirmatory data set 300 will also be determined and stored in datastorage 17 (Block 506). As will be understood, typically an ion willfragment into a plurality of ion fragments. Accordingly, in manyinstances, the confirmatory data couplets 302 corresponding to a triggercouplet 202, will share the same precursor ion 204, 304.

As will be understood, the trigger data 200 (designated precursor ion(s)204 and designated ion fragment(s) 206, together with the correspondingtrigger time window 208) and the related confirmatory data 300 fornumerous analytes of interest may be previously calculated and stored asa library of data in the data storage 17, and simply indexed andretrieved by the user and the CPU 12 utilizing the I/O device 16.

The duty cycle list 400 is initiated, being populated with couplets 402of designated precursor ion 204 and designated ion fragment 206 from thetrigger data 200 which have a trigger time window 208 which commences orcoincides with the beginning of the analysis period. FIG. 4A illustratesan example duty cycle list 400 as one may exist at the commencement ofan analysis period. The user will then typically input a command tocommence an analysis period (typically via the I/O device 16), uponreceipt of which the trigger engine 14 is programmed to initiate theanalysis period (Block 510).

When the analysis period is commenced, the ion source 20 is activated tocommence the emitting of ions from the sample 21 (which may be thecommencement of the LC phase as outlined above)(Block 512). As will beunderstood, the sample compound, for example, may include bodily fluidtaken from a test subject, which fluid often includes both drugmetabolites of interest, as well as irrelevant endogenous ions from thetest subject.

The system 10 is then configured to selectively filter the emitted ionsfor the designated precursor ions 404 listed on the duty cycle listing400 (Block 514). As will be understood, at least one (if not most) ofthe precursor ions 404 (and designated ion fragments 406) listed on theduty cycle listing 400 corresponds to a trigger ion 204 (and trigger ionfragment 206) in the trigger data 200. As indicated by the dotted line530, the CPU 12/trigger engine 14 is programmed to rapidly andrepeatedly cycle through the designated precursor ions 404 on the dutycycle listing, and causes the rod set Q1 to selectively filter the ionsreceived from the ion source 20 for the designated precursor ions 404.

The filtered ions 404 (which as noted, include at least one trigger ion204), are then received by the fragmentation module/rod set Q2 andfragmented (Block 516). The fragments are then received by the Q3 rodset, which is controlled by the trigger engine 14 to scan or filter forthe designated ion fragments 406 on the duty cycle listing 400 (Block518). Such designated ion fragments 406 (if any) are permitted to impactthe detector 22. As will be understood, the filtering, fragmenting andfiltering steps of Blocks 514-518 are typically all performed for oneion/fragment couplet 402, prior to the trigger engine 14 cycling to thenext couplet 402 on the duty cycle list 400.

If the detector 22 detects a designated trigger ion fragment 206 (Block522), the trigger engine 14 may be programmed to cause the system 10 toscan for at least one confirmatory ion fragment. As will be understood,a certain threshold may be predetermined for “detecting” a trigger ionfragment 206—a certain quantity of trigger ion fragments 206 must bedetected in order for the trigger ion fragment 206 to be considered“detected”. Similarly, in the event multiple trigger ion 204/fragment206 couplets in a trigger entry 202 must be “detected” the triggerengine 14 may be programmed to determine that such multiple trigger ion204/fragment 206 couplets have been detected before the system 10 scansfor confirmatory ion fragment(s).

The trigger engine 14 determines the confirmatory entry identifier 210corresponding to the designated trigger ion fragment 206 (and designatedtrigger ion 204), and adds to the duty cycle listing 400 the one or morecorresponding confirmatory couplets 302 of confirmatory ion 304 andconfirmatory ion fragment 306 (linked to by the matching identifiers210, 310) and calculates or otherwise determines the scanning windowdata 408 which is also added to the duty cycle listing 400 (Block 524).Referring briefly again to FIGS. 4A and 4B, the example data provides anillustrative example of the updating of a duty cycle listing 400, 400′,after the designated ion 204/designated trigger ion fragment 206 couplet202′, has been detected. The designated confirmatory ion 304 anddesignated confirmatory ion fragment 306 data in the correspondingconfirmatory entry 302′ (sharing a matching confirmatory identifier 310,210 with the detected trigger couplet 202′) have been added as entries402* to the duty cycle listing 400′, together with the calculatedtrigger window data 408. As can be seen from the example calculatedtrigger window data 408* for the added entries 402*, the trigger engine14 has detected the couplet 202′ at approximately 5 seconds from thecommencement of the analysis period and has calculated the triggerwindow data 408* as commencing at the time of detection, 5 seconds, forthe duration of the corresponding scanning window duration 308 (in thiscase 3 seconds), to result in an entry 408* of “5 sec.-8 sec.”, as willbe understood.

Over time, as the time of the analysis period advances as may be trackedby the clock module 18, the duty cycle listing is updated (Block 526).As the analysis period moves into the various trigger time windows 208,the corresponding couplet 202 of designated trigger ions 204 and ionfragments 206 are added to the duty cycle listing 400. Similarly, as thetime of the analysis period moves beyond the various trigger timewindows 408, the corresponding couplet 402 of designated ions 404 andion fragments 406 are removed from the duty cycle listing 400.

As will be understood, during the updating carried out in Block 526,when a trigger time window 408 has passed and the corresponding couplet202, 402 of designated trigger ions 204, 404 and ion fragments 206, 406are removed from the duty cycle listing 400, as well the correspondingconfirmatory couplet(s) 302 of confirmatory ion(s) 304, 404 and ionfragment(s) 306, 406 are removed from the duty cycle listing 400. Theprocess cycles through the various steps 514-526 until the analysisperiod is complete and ion emission is terminated.

Thus, for example, by referring to both FIGS. 4A and 4B, it is possibleto compare the duty cycle listing 400 at or near the commencement of theanalysis period to the duty cycle listing 400′ as it may appear atapproximately 7 seconds into the analysis period for the exemplary data.As can be seen, since the scanning window 408 for the ion/fragmentcouplet pointed to by 402′ has passed, this couplet 402′ has beenremoved from the duty cycle listing 400′. Similarly, as the analysistime has moved into the range of trigger or scanning windows 208, forion/fragment couplets 202″ in the trigger data set 200, suchcorresponding couplets 402″ have been added to the duty cycle listing400′. As will be understood, the updating step of Block 526 will beunnecessary for applications which do not involve trigger or scanningwindows.

As will be understood, the controller 12 may generate a reportidentifying the quantities of the various designated ion/fragmentcouplets and hence the presence or absence of the corresponding analytesof interest (Block 528). Quantities of confirmatory couplets 302 shouldapproximate the quantities of the corresponding trigger couplets 202,confirming both the quantity and presence of the corresponding analytesof interest, as will be understood.

Thus, while what is shown and described herein constitute preferredembodiments of the subject invention, it should be understood thatvarious changes can be made without departing from the subjectinvention, the scope of which is defined in the appended claims.

1. A method of analyzing a sample, comprising: (a) emitting ions fromthe sample; (b) selectively filtering the emitted ions for at least onedesignated trigger ion; (c) fragmenting the designated trigger ions; (d)scanning for a designated trigger ion fragment; and (e) upon detectingthe designated trigger ion fragment, scanning for at least oneconfirmatory ion fragment.
 2. The method as claimed in claim 1, wherein(b) through (e) are performed during a trigger time window correspondingto the designated trigger ion.
 3. The method as claimed in claim 2,wherein the trigger time window is selected to correspond to a timeperiod when the trigger ion is expected to be emitted from the sample.4. The method as claimed in claim 1, wherein (b) through (e) areperformed for a plurality of designated trigger ions during a pluralityof trigger time windows, each trigger time window corresponding to adesignated trigger ion.
 5. The method as claimed in claim 4, whereineach trigger time window is selected to correspond to a time period whenthe corresponding trigger ion is expected to be emitted from the sample.6. The method as claimed in claim 4, wherein during the method, (d) isperformed substantially simultaneously for at least two differentdesignated trigger ion fragments.
 7. The method as claimed in claim 1,further comprising generating a report containing data corresponding tothe detected designated trigger ion fragments and confirmatory ionfragments.
 8. The method as claimed in claim 1, wherein (a) is performedusing liquid chromatography.
 9. Computer readable media configured tocause a mass spectrometer having a computer controller to perform themethod of claim 1.